Contemporary Analysis of Prognostic Factors in Patients with Unresectable Malignant Pleural Mesothelioma

Our plain-English summary of Contemporary Analysis of Prognostic Factors in Patients with Unresectable Malignant Pleural Mesothelioma, by A. Billé, L.M. Krug, K.M. Woo, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: A. Billé, L.M. Krug, K.M. Woo, V.W. Rusch, M.G. Zauderer
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(2):249-55
• Cited by: 60 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Previous prognostic scoring systems for malignant pleural mesothelioma (MPM) included patients managed surgically and predated the use of pemetrexed. We analyzed prognostic factors in a contemporary cohort of patients with unresectable MPM who received pemetrexed-based chemotherapy.

Methods: This single-institution analysis included patients with MPM who were managed nonsurgically from 2000 to 2013. Variables correlated with overall survival (OS) included sex, performance status (PS), asbestos exposure, tumor laterality, histology, clinical stage, initial positron emission tomography maximum standardized uptake value, hemoglobin level, platelet count, lymphocyte count, white cell and neutrophil counts, treatment type, and clinical benefit from treatment. OS was analyzed by the Kaplan-Meier method, and significance (p < 0.05) of prognostic factors was analyzed by the log-rank test and Cox regression.

Results: A total of 191 patients met the study criteria: median age 71 years (range 46-90), 147 men (77%), 128 epithelioid tumors (67%), and 157 cases of stage III or IV MPM (82%). Median OS for all patients was 13.4 months. According to a univariate analysis, histology (p < 0.001), platelet count (< or = 450,000 versus >450,000, p < 0.001), initial PS (0-1 versus > or = 2), maximum standardized uptake value (< or = 8.1 versus >8.1, p = 0.037), and lymphocyte counts (p = 0.019) were associated with OS. According to a multivariable analysis, only histology, platelet count, and PS were independent prognostic factors. Epithelioid histology, PS, and elevated lymphocyte count at diagnosis were significantly associated with clinical benefit from first-line chemotherapy.

Conclusions: Our results confirm the significance of elements of the Cancer and Leukemia Group B and European Organisation for Research and Treatment of Cancer prognostic scoring systems, identify factors associated with clinical benefit from chemotherapy, and emphasize the impact of histology and clinical benefit of chemotherapy on outcomes.

Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective review of medical records at Memorial Sloan Kettering Cancer Center, New York, covered patients with malignant pleural mesothelioma whose tumors were not surgically removed, treated 2000 to 2013. Of 413 patients, 191 met the study criteria. Most who had chemotherapy received pemetrexed. Median overall survival for all 191 patients was 13.4 months (95% CI 12.4–15.7). Documented asbestos exposure (104 patients) was not significantly associated with survival. In a combined (multivariate) analysis of 140 patients, three factors were independently linked to shorter survival: biphasic or sarcomatoid versus epithelioid tumor type (hazard ratio 2.96, 95% CI 1.91–4.57), platelets above 450,000 per mm3 versus at or below (2.09, 1.33–3.35), and ECOG performance status 2–3 versus 0–1 (1.83, 1.23–2.74). Measured from the start of treatment, patients who gained clinical benefit from first-line chemotherapy had a median survival of 16.8 months (95% CI 14.8–20.1), against 6.5 months (5.4–8.5) without benefit. Benefit was more common with good performance status, epithelioid tumors and higher lymphocyte counts. The authors concluded their results confirm some elements of two earlier prognostic scoring systems.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of medical records at a single institution (survival analysis of prognostic factors)
• Who was studied: 191 of 413 patients with malignant pleural mesothelioma treated at Memorial Sloan Kettering Cancer Center, New York, between January 2000 and December 2013. All were managed without surgical removal of the tumor. Median age was 71; 147 (77%) were men; 128 (67%) had epithelioid tumors; 157 (82%) had stage III or IV disease. Patients with peritoneal mesothelioma were excluded.
• Exposure: The study examined prognostic factors, not asbestos as a cause. Documented asbestos exposure was one variable: 104 patients (54%) exposed, 86 (45%) not, 1 unknown. No fiber types were given. Treatments included chemotherapy (90% of those treated received pemetrexed), radiotherapy, or supportive care.
• Main results:
  • Median overall survival for all 191 patients was 13.4 months (95% CI 12.4–15.7).
  • Asbestos exposure was not significantly associated with overall survival (p = 0.35). Median survival was 12.6 months (95% CI 10.8–15.2) in patients with documented exposure and 14.9 months (95% CI 12.7–19.3) in those without.
  • Patients with epithelioid mesothelioma had a median survival of 17.0 months (95% CI 14.3–19.4) and a 1-year survival of 69%. Patients with biphasic or sarcomatoid mesothelioma had 9.6 months (95% CI 7.5–11.4) and 29%.
  • Patients with a platelet count of 450,000 per mm3 or less had a median survival of 15.2 months (95% CI 13.3–17.9) and a 1-year survival of 65%. Patients with a count above 450,000 had 9.0 months (95% CI 7.6–11.6) and 32%.
  • Patients with good performance status (ECOG 0 or 1) had a median survival of 16.0 months (95% CI 13.3–18.9, per Table 2) and a 1-year survival of 64%. Patients with poor performance status (ECOG 2 or 3) had 10.1 months (95% CI 7.9–13.1) and 42%.
  • The multivariate analysis included 140 patients, and three factors were independent prognostic factors. Biphasic or sarcomatoid versus epithelioid histology: hazard ratio 2.96 (95% CI 1.91–4.57). Platelets above 450,000 per mm3 versus at or below: HR 2.09 (1.33–3.35). ECOG performance status 2–3 versus 0–1: HR 1.83 (1.23–2.74). SUVmax on PET, neutrophil count and lymphocyte count were not independent factors.
  • Survival here was measured from the start of treatment. Patients who had clinical benefit from first-line chemotherapy had a median survival of 16.8 months (95% CI 14.8–20.1), against 6.5 months (95% CI 5.4–8.5) for those who did not. Their 1-year survival rates were 70% and 22%.
  • Clinical benefit from chemotherapy was seen in 64% of patients with good performance status and 36% of those with poor performance status. It was seen in 63% of patients with epithelioid tumors and 45% of those with sarcomatoid tumors.
  • Clinical benefit was seen in 67% of patients with a lymphocyte count above 1400 cells per microliter and 46% of those below 1400. Sex, clinical stage, SUVmax and platelet count were not associated with clinical benefit.
• The authors' conclusion: The authors concluded that some elements of the earlier CALGB and EORTC prognostic scoring systems correlate with survival in this group of patients with unresectable disease who mostly received pemetrexed-based therapy. They also concluded that they had identified factors associated with clinical benefit from chemotherapy.
• Limitations the authors state:
  • Tumor type was determined from small biopsy samples, so a tumor called epithelioid might actually have been of mixed type.
  • The analyses of sex and age may have been confounded by the small numbers of young patients and women in the study.
  • The PET analysis was limited because some patients had pleurodesis before their PET scan, and not all scans were done at the same center.
  • The better survival seen with second-line chemotherapy may be confounded, because patients who lived longer were more likely to receive more chemotherapy.
  • Clinical staging of mesothelioma is inaccurate.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Unresectable, Pleural Mesothelioma, Pemetrexed (Alimta), Chemotherapy, Overall Survival, Performance Status, Asbestos Exposure, Histology.

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• Survival and prognostic factors in malignant pleural mesothelioma: a retrospective study of 314 patients in the west part of Japan — S. Nojiri, K. Gemba, et al. (2011)
• Validation of prognostic factors in malignant pleural mesothelioma: a retrospective analysis of data from patients seeking compensation from the New South Wales Dust Diseases Board — S.C. Kao, J. Vardy, et al. (2013)
• Serum albumin as a significant prognostic factor in patients with malignant pleural mesothelioma — Z.H. Yao, G.Y. Tian, et al. (2014)
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